Primary Objectives:

• To document the efficacy of treatment with autologous lymphoma-derived HSPPC-96 of selected patients with indolent lymphoma. The efficacy endpoints are:
• the rate of complete and partial responses
• the time to progression.

Secondary Objectives:

• To evaluate the safety and tolerability of autologous tumor-derived heat-shock protein peptide complex (HSPPC-96) administered intradermally once weekly for four consecutive weeks, followed by HSPPC-96 administered once every two weeks.
• To evaluate the feasibility of autologous HSPPC-96 preparation from lymphoma specimens.
• To assess approximately the composition of the tissue source of the autologous HSPPC-96 for each patient.
• To study the effect of autologous lymphoma-derived HSPPC-96 vaccine therapy on the expression of Fas ligand and TRAIL death proteins in peripheral blood lymphocytes of patients with indolent lymphoma.

Inclusion Criteria:

• Patients with previously treated or newly diagnosed follicular center cell grade I or grade II lymphoma, small lymphocytic lymphoma, MALT lymphoma, monocytoid B-cell lymphoma, Waldenstrom's macroglobulinemia, or marginal zone lymphoma with bidimensionally measurable disease;
• Part of the resected specimen must undergo routine pathologic examination to confirm the diagnosis of lymphoma. The remaining tissue must be used for the preparation of autologous HSPPC-96;
• Autologous HSPPC-96 vaccine must be successfully prepared and provided by the sponsor;
• A minimum of 2 grams of non-necrotic, resectable malignant lymphoma for HSPPC-96 preparation;
• Bidimensionally measurable disease in at least one location other than the resected lymphoid tissue;
• Life expectancy of at least 16 weeks;
• Zubrod performance status of less then or equal to 2;
• Adequate bone marrow function;
• Adequate hepatic function;
• Adequate renal function;
• Signed written informed consent;
• Patients of child-bearing potential must practice contraception, which is adequate in the opinion of the Principal Investigator;
• Patients of child-bearing potential must have a negative serum pregnancy test prior to entry into the study and must not be lactating;
• Patients must be willing to be followed at the M. D. Anderson Cancer Center during the course of treatment and follow-up;
• Electrocardiogram if none performed in the prior six months;
• Patients must have no chemotherapy, immunotherapy, radiotherapy, or experimental anti-cancer therapy within six weeks prior to starting autologous HSPPC-96 administration;
• Patients must have fully recovered from prior anti-cancer therapy;
• Tumor measurements and staging no more than 4 weeks prior to receiving the first dose of autologous HSPPC-96.

Exclusion Criteria:

• Patients with active or prior history of central nervous system lymphoma;
• Patients with serious intercurrent medical illnesses, requiring hospitalization;
• Patients with a history of primary or secondary immunodeficiency (other than related to the malignant lymphoma because treatment is dependent on functional immune system) or patients taking immunosuppressive drugs such as systemic corticosteroids;
• Women who are pregnant or lactating;
• Patients participating in another clinical trial;
• Patients receiving growth factors of any kind, including G-CSF, GM-CSF, or Epogen;
• Patients with bulky disease, defined as greater than 10 cm in diameter;
• Patients with positive HIV antibody;
• Patients with more than 4 previous treatment regimens will be excluded.